Abstract

Lysosomal storage diseases are a group of disorders where accumulation of catabolites
is manifested in the lysosomes of different cell types. In metachromatic leukodystrophy
(Arylsulfatase A [EC.3.1.6.8] deficiency) storage of the glycosphingolipid sulfatide
in the brain leads to demyelination, resulting in neuromotor co-ordination deficits
and regression. In a mouse model for metachromatic leukodystrophy, the ASA null mutant
mouse, the accumulation of sulfatide in correlation to phenotype has been thoroughly
investigated. Another lipid species reported to accumulate in patients with metachromatic
leukodystrophy is the sulfatide related lipid lysosulfatide. Lysosulfatide was shown
to be a cytotoxic compound in cell culture experiments and thus suggested to be involved
in the pathology of metachromatic leukodystrophy. In this study, we further investigated
the developmental profile of lysosulfatide in the brain of ASA null mutant mice by
using high performance liquid chromatography. Lysosulfatide could be detected in the
brain of normal mice (ASA +/+) from 1.8 months up to 23.1 months of age. From the
age of 8.8 months the lysosulfatide levels remained constant at 1 pmol/mg wet tissue.
The developmental change (< 20 months) of brain lysosulfatide showed an accumulation
in ASA null mutant mice at ages above one month compared to its normal counterpart
(ASA +/+). Thus, the ASA null mutant mouse might be a suitable model to further investigate
the role of lysosulfatide in the pathogenesis of metachromatic leukodystrophy.